A General Strategy for Site-Selective Incorporation of Deuterium and Tritium Into Pyridines, Diazines, and Pharmaceuticals

J Am Chem Soc. 2018 Feb 14;140(6):1990-1993. doi: 10.1021/jacs.7b11710. Epub 2018 Feb 5.


Methods to incorporate deuterium and tritium atoms into organic molecules are valuable for medicinal chemistry. The prevalence of pyridines and diazines in pharmaceuticals means that new ways to label these heterocycles will present opportunities in drug design and facilitate absorption, distribution, metabolism, and excretion (ADME) studies. A broadly applicable protocol is presented wherein pyridines, diazines, and pharmaceuticals are converted into heterocyclic phosphonium salts and then isotopically labeled. The isotopes are incorporated in high yields and, in general, with exclusive regioselectivity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Deuterium / chemistry*
  • Heterocyclic Compounds / chemistry*
  • Isotope Labeling / methods
  • Organophosphorus Compounds / chemistry
  • Pharmaceutical Preparations / chemistry*
  • Pyridines / chemistry*
  • Stereoisomerism
  • Tritium / chemistry*


  • Heterocyclic Compounds
  • Organophosphorus Compounds
  • Pharmaceutical Preparations
  • Pyridines
  • Tritium
  • Deuterium